Mechanically strong absorbable polymeric blend compositions of precisely controllable absorption rates, processing methods, and products therefrom

ABSTRACT

Novel absorbable polymer blends are disclosed. The blends are useful for manufacturing medical devices having engineered degradation and breaking strength retention in vivo. The blends consist of a first absorbable polymeric component and a second absorbable polymeric component. The weight average molecular weight of the first polymeric component is higher than the weight average molecular weight of the second polymeric component. At least at least one of said components is at least partially end-capped by a carboxylic acid group. Further aspects are medical devices made therefrom.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of co-pending application Ser. No.13/833,690 filed on Mar. 15, 2013 which claims priority to U.S.Provisional application 61/651,353 filed May 24, 2012.

FIELD OF THE INVENTION

The field of art to which this invention relates is absorbable polymers,in particular, absorbable polymer blends useful for manufacturingmedical devices, especially sutures, possessing high initial mechanicalstrength and controlled loss of mechanical properties post-implantationand/or controlled absorption time.

BACKGROUND OF THE INVENTION

Absorbable polymers and medical devices made from such polymers areknown in the art. Conventional absorbable polymers include polylacticacid, poly(p-dioxanone), polyglycolic acid, co-polymers of lactide,glycolide, p-dioxanone, trimethylene carbonate, ε-caprolactone, invarious combinations, etc. The chemistry of absorbable polymers isdesigned such that the polymers breakdown in vivo, for example byhydrolysis, and the byproducts metabolized or otherwise excreted fromthe patient's body. The advantages of utilizing implantable medicaldevices made from absorbable polymers are numerous and include, forexample, eliminating the need for additional surgeries to remove animplant after it serves its function. In the case of a wound closurefunction, when a “temporary presence” of the implant is desired, ideallysupport can be provided until the tissue heals.

Absorbable is meant to be a generic term, which may also includebioabsorbable resorbable, bioresorbable, degradable or biodegradable.

The absorbable polymers conventionally used to manufacture medicaldevices have been on occasion polymeric blends of absorbable polymersand co-polymers engineered to provide specific characteristics andproperties to the manufactured medical device, including absorptionrates, mechanical property (e.g., breaking strength) retentionpost-implantation, and dimensional stability, etc.

There are many conventional processes used to manufacture medicaldevices from absorbable polymers and polymer blends. The processesinclude injection molding, solvent casting, extrusion, machining,cutting and various combinations and equivalents. A particularly usefuland common manufacturing method is thermal forming using conventionalinjection molding processes and extrusion processes.

The retention of mechanical properties post-implantation is often a veryimportant feature of an absorbable medical device. The device mustretain mechanical integrity until the tissue has healed sufficiently. Insome bodily tissues, healing occurs more slowly, requiring an extendedretention of mechanical integrity. This is often associated with tissuethat has poor vascularization. Likewise there are other situations inwhich a given patient may be prone to poor healing: e.g., the diabeticpatient. There are however many situations in which rapid healingoccurs, which require the use of fast absorbing medical devices such assutures; this is often associated with excellent vascularization.Examples of where such fast absorbing sutures can be used includecertain pediatric surgeries, oral surgery, repair of the peritoneumafter an episiotomy and superficial wound closures.

When rapid healing occurs, the mechanical retention profile of themedical device could reflect a more rapid loss in properties.Concomitant with this is the rate of absorption (bioabsorption orresorption), that is, the time required for the medical device todisappear from the surgical site.

One method that has been exploited to achieve the rapid loss ofmechanical properties is the use of pre-hydrolysis and/or gammairradiation. For instance Hinsch et al., in EP 0 853 949 B1, describe aprocess for reducing the resorption period of hydrolyzable resorbablesurgical suture material, wherein the surgical suture material isincubated in a hydrolysis buffer, having an index of pH in the rangefrom 4 to 10, for a period in the range from 10 hours to 100 hours at atemperature in the range from 30° C. to 65° C.

In order to shorten the absorption period of absorbable suture materialit is also known to irradiate the suture material during themanufacture, e.g., by means of Co-60 gamma irradiation. Such anirradiation process produces defects in the polymer structure of thesuture material, resulting in an accelerated decrease of the tensilestrength and a shortened absorption period in vivo after implantation ofthe suture material. To use gamma irradiation in a manufacturingenvironment in order to reliably adjust in vivo absorption times andcontrol post-implantation mechanical property loss is often difficultdue to a variety of reasons. These reasons include the high precisionrequired, and, the unintended damage to other important properties suchas discoloration.

It is well known, however, that such treatments of pre-hydrolysis andgamma irradiation may have a negative effect on the mechanicalproperties of the device. Consequently, and for example, sutures thatare touted as fast absorbing are often lower in initial strength thantheir standard absorbing suture counterparts.

In certain surgical procedures, the mechanical properties, particularlythe tensile strength, of the wound closure device are clinically veryimportant; in these wound closure devices, such as sutures, highstrength is generally preferred. Commercially available braided fastabsorbing suture sold by ETHICON, Inc., Somerville, N.J. 08876, andknown as VICRYL RAPIDE™ (polyglactin 910) Suture exhibits a tensilestrength of about 60 percent of the standard absorbing counterpart,Coated VICRYL™ (polyglactin 910) Suture.

There is a continuing need in this art for novel medical devices thatlose their mechanical properties quickly and are absorbed rapidly, butwhich still provide high initial mechanical properties approaching thoseexhibited by their standard absorbing counterparts.

There have been attempts in the prior art to address the problem ofrapid absorption. Rose and Hardwick in U.S. Pat. No. 7,524,891 describethe addition of certain carboxylic acids and their derivatives andanhydrides to poly(lactic acid) to make homogeneous blends, whichexhibit a more rapid absorption. It should be noted that that they limitthe amount of the additive to 10 weight percent. They clearly describe asystem in which the additive is admixed throughout and is not reactivewith the poly(lactic acid) so as to create a derivative.

There have been attempts in the prior art to address the problem ofimproved strength. For instance, Brown in US Patent ApplicationPublication No. 2009/0274742 A1, entitled “Multimodal High StrengthDevices And Composites”, (hereinafter referred to as “'742”) disclosesan oriented implantable biodegradable multimodal device comprising ablend of a first polymer component having a first molecular weighttogether with at least a second polymer component having a molecularweight which is less than that of the first component, wherein polymercomponents within the blend are in uniaxial, biaxial or triaxialorientation. Brown speaks of achieving higher mechanical properties inblends of high molecular weight polylactide (e.g., IV=4.51 dL/g) withmuch lower molecular weight versions of this polymer (Mw=5,040 Da,Mn=3,827 Da), but only shows an increase in modulus and no increase inmaximum stress. Additionally, Brown in '742 mentions a faster rate ofabsorption as compared to the high molecular weight polylactide when anadditive is admixed in an amount of not more than 10% by weight of thepolymer components.

A bimodal bioabsorbable polymer composition is disclosed in US PatentApplication Publication US 2007/0149640 A1. The composition includes afirst amount of a bioabsorbable polymer polymerized so as to have afirst molecular weight distribution and a second amount of saidbioabsorbable polymer polymerized so as to have a second molecularweight distribution having a weight average molecular weight betweenabout 20,000 to about 50,000 Daltons. The weight average molecularweight ratio of said first molecular weight distribution to said secondmolecular weight distribution is at least about two to one, wherein asubstantially homogeneous blend of said first and second amounts of saidbioabsorbable polymer is formed in a ratio of between about 50/50 toabout 95/5 weight/weight percent. Also disclosed are a medical deviceand a method of making a medical device.

In US 2009/0118241 A1, a bimodal bioabsorbable polymer composition isdisclosed. The composition includes a first amount of a bioabsorbablepolymer polymerized so as to have a first molecular weight distributionand a second amount of said bioabsorbable polymer polymerized so as tohave a second molecular weight distribution having a weight averagemolecular weight between about 10,000 to about 50,000 Daltons. Theweight average molecular weight ratio of said first molecular weightdistribution to said second molecular weight distribution is at leastabout two to one, wherein a substantially homogeneous blend of saidfirst and second amounts of said bioabsorbable polymer is formed in aratio of between about 50/50 to about 95/5 weight/weight percent. Alsodisclosed are a medical device, a method of making a medical device anda method of melt blowing a semi-crystalline polymer blend.

Even though such polymer blends are known, there is a continuing need inthis art for novel absorbable polymeric materials having preciselycontrollable absorption rates, that provide a medical device withimproved characteristics including stiffness, retained strength in vivo(in situ), dimensional stability, absorbability in vivo, andmanufacturability; there is a particular need for accelerated absorptionand accelerated mechanical property loss post-implantation while stillexhibiting high initial mechanical properties.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide novel absorbablepolymer blends that can be used in manufacturing processes to producenovel absorbable medical devices and medical device components by meltprocesses, such as extrusion or injection molding. When the medicaldevice is in the form of a suture, said suture has superior mechanicalproperties (e.g., high breaking strength) at the time of implantation,as well as during the critical wound healing period, which is forexample about 5 to 7 days post-implantation, when compared to aconventional suture with comparable composition. Once said criticalwound healing period is over, said suture exhibits a rapid butcontrolled loss of mechanical properties within, for exampleapproximately 14 days post-implantation, and a rapid but controlledabsorption within, for example, approximately 42 days post-implantation.

Accordingly, a novel absorbable polymer blend composition is disclosed.The polymer blend is a mixture of a first absorbable polymeric componentand a second absorbable polymeric component, wherein the first polymericcomponent has a weight average molecular weight higher than the weightaverage molecular weight of the second polymeric component, and whereinat least one of said components is at least partially end-capped by acarboxylic acid group.

The second polymeric component having lower weight average molecularweight can be also characterized as an oligomer or an oligomericcomponent.

In one aspect of the present invention, the absorbable polymer blendcomprises a first absorbable polymeric component comprising about 65weight percent to about 97.5 weight percent of a glycolide polymer or alactide/glycolide copolymer containing about 0 mol percent to about 20mol percent of polymerized lactide, and about 80 mol percent to about100 mol percent of polymerized glycolide. The second absorbablepolymeric component is a glycolide polymer or a lactide/glycolidecopolymer containing about 0 mol percent to about 20 mol percent ofpolymerized lactide, and about 80 mol percent to about 100 mol percentof polymerized glycolide.

Another aspect of the present invention is a thermally processedabsorbable polymer blend composition. The polymer blend has a firstabsorbable polymer component and a second absorbable polymer component.Wherein, the first polymeric component has a weight average molecularweight higher than the weight average molecular weight of the secondpolymeric component, and wherein at least one of said components is atleast partially end-capped by a carboxylic acid group.

Yet another aspect of the present invention is a novel absorbablemedical device. The medical device comprises an absorbable polymer blendof a first absorbable polymer component and a second absorbable polymercomponent. Wherein, the first polymeric component has a weight averagemolecular weight higher than the weight average molecular weight of thesecond polymeric component, and wherein at least one of said componentsis at least partially end-capped by a carboxylic acid group.

Still yet another aspect of the present invention is a method ofmanufacturing a medical device. The method includes the steps ofprocessing an absorbable polymer blend. The polymer blend has a firstabsorbable polymer component and a second absorbable polymer component.Wherein, the first polymeric component has a weight average molecularweight higher than the weight average molecular weight of the secondpolymeric component, and wherein at least one of said components is atleast partially end-capped by a carboxylic acid group.

Further aspects of the present invention include the above-describedmedical device and method, wherein the polymer blend is thermallyprocessed. The blend can be made by thermal processes and articles canbe made from the blend by thermal processes.

These and other aspects and advantages of the present invention willbecome more apparent from the following description and accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1D illustrate various braided suture constructions.

FIG. 2 is an illustration of a monofilament suture alongside a surgicalneedle.

FIG. 3 is an illustration of a molded surgical tack.

FIG. 4 is a plot of breaking strength as a function of implantation timefor a normally absorbing prior art poly(lactide-co-glycolide)multifilament suture, a prior art rapidly absorbingpoly(lactide-co-glycolide) multifilament suture, and a rapidly absorbingpoly(lactide-co-glycolide) multifilament suture of the presentinvention.

FIG. 5 is a plot of the time required in an aqueous buffer at a pH of7.27 and 37 degree centigrade for a poly(lactide-co-glycolide)multifilament suture to achieve a drop in initial breaking strength of50 percent, as a function of the acid level present.

FIG. 6 is a plot of the time required in an aqueous buffer at a pH of7.27 and 37 degree centigrade for a poly(lactide-co-glycolide)multifilament suture to achieve a drop in initial breaking strength of100 percent, as a function of the acid level present.

FIG. 7 is a plot of maximum acid level vs. the value of IR₂.

DETAILED DESCRIPTION OF THE INVENTION

It should be clear to one having ordinary skill in the art that acidlevel might be expressed by a variety of methods. These includemilliequivalents per gram (meq/gram). We intend to define the concept ofan acid level to be used herein. One determines the number of moles ofcarboxylic acid groups attached to the chains of the resin underconsideration. If the resin is a polylactone, one determines the numberof moles of lactone monomer incorporated into said resin. The acid levelis herein defined as the number of moles of said carboxylic acid groupsattached to the chains, divided by the number of moles of said lactonemonomer incorporated into said resin. In the case of resins containingpolymeric repeat units not formed from lactones, the number of moles ofrepeat units will be included.

Thus if a resin was formed containing 90 moles of polymerized glycolideand 10 moles of polymerized lactide, and had end groups corresponding to1.7 moles of carboxylic acid groups, one could calculate that the resinhad an acid level of 1.7 percent [100×1.7/(90+10)=1.7]. In anotherexample, if a resin was formed containing 81 moles of polymerizedglycolide, 9 moles of polymerized lactide, and 10 moles of repeat unitsof hexamethylene adipate, and had end groups corresponding to 2.0 molesof carboxylic acid groups, one could calculate that this second resinhad an acid level of 2.0 percent [100×2.0/(81+9+10)=2.0].

For a surgical suture based on a polyglycolide or a glycolide-richcopolymer, the minimum acid level is 0.3 percent and the maximum acidlevel that can be incorporated and still allow high mechanicalproperties is dependent on the molecular weight of the lower molecularweight blend component. When the lower molecular weight component isblended with a higher molecular weight blend component possessing aweight average molecular weight of 80,000 Daltons, the maximum acidlevel limit is approximately 12 percent when the initiator ratio for thelower molecular weight blend component value, IR₂, is 10; when IR₂ is20, the maximum acid level limit is approximately 6 percent.

We have determined that when the lower molecular weight component isblended with a higher molecular weight blend component possessing aweight average molecular weight of 80,000 Daltons, the maximum acidlevel limit as a function of the initiator ratio for the lower molecularweight blend component value, IR₂, can be described by the followingexpression:Max acid level=110×IR ₂ ^(−0.983)  (1)

We have determined that when the lower molecular weight component isblended with a higher molecular weight blend component possessing aweight average molecular weight of 120,000 Daltons, the maximum acidlevel limit as a function of the initiator ratio for the lower molecularweight blend component value, IR₂, can be described by the followingexpression:Max acid level=140×IR ₂ ^(−0.994)  (2)

The initiator ratio, IR, is defined as the ratio of moles of initiatordivided by the total moles of monomers. IR₁ refers to the initiatorratio of the first blend component and IR₂ refers to the initiator ratioof the second blend component.

In some embodiments of the present invention, IR₁ values can range fromabout 250 to about 1200 and IR₂ values can range from about 8 to about100.

Thus the maximum amount of acid that can be incorporated into the novelblends of the present invention is dependent on the IR₂ value, as wellas the molecular weight of the higher molecular weight blend component.So when the value of IR₂ is 10, the maximum acid value is about 12percent when the weight average molecular weight of the high molecularweight component is 80,000 Daltons, is about 14 percent when the weightaverage molecular weight of the high molecular weight component is120,000 Daltons. Correspondingly, when the value of IR₂ is 20, themaximum acid value is about 6 percent when the weight average molecularweight of the high molecular weight component is 80,000 Daltons, isabout 7 percent when the weight average molecular weight of the highmolecular weight component is 120,000 Daltons.

With lower values of IR₂, higher a maximum acid levels are possible. Forinstance, maximum acid levels of about 20 percent when the firstpolymeric component has a weight average molecular weight of 80,000Daltons, and wherein the maximum acid level is about 26.5% when thefirst polymeric component has a weight average molecular weight of120,000 Daltons.

The novel polymer blends of the present invention are made fromabsorbable polyester (co)polymers and (co)oligomers. Preferably, one ofthe blend components is a glycolide/lactide co-polymer. Another blendcomponent is a glycolide/lactide co-oligomer with a substantial numberof endgroups acidic in nature.

The glycolide/lactide copolymer will be manufactured in a conventionalmanner. A preferred manufacturing method is as follows. Lactone monomersare charged along with an alcohol initiator, a suitable catalyst, anddye if desired, into a conventional stirred pot reactor. After purgingto remove oxygen, under a nitrogen atmosphere, the reactants are heatedwith agitation to conduct a ring-opening polymerization. After asuitable time the formed resin is discharged and sized appropriately.The resin particles are subjected to a devolatilization process and aresubsequently stored under vacuum. The mole percent of polymerizedglycolide and polymerized lactide in the glycolide-rich co-polymeruseful in the novel blends of the present invention may be varied toprovide desired characteristics. Typically, the mole percent ofpolymerized glycolide in the glycolide-rich polymer will be about 80percent to about 100 percent, more typically about 85 percent to about95 percent, and preferably about 88 percent to about 92 percent. Whenthe polymerized glycolide in the glycolide-rich polymer is 100 percent,the polymer is polyglycolide; polyglycolide is preferred for somesurgical applications. Typically, the mole percent of polymerizedlactide in the glycolide-rich co-polymer will be about 0 percent toabout 20 percent, more typically about 5 percent to about 15 percent,and preferably about 8 percent to about 12 percent.

We have found that the polymers of the present invention can be madeutilizing metal-based catalysts such as tin catalysts or titaniumcatalysts. Tin catalysts include stannous octoate and stannous chloride.We have additionally found that the level of catalyst is advantageouslyin the range of about 3 to 30 ppm, based on the metal content.

The respective amounts of the higher and lower molecular weightpolymeric components present in the novel blends of the presentinvention will be sufficiently effective to provide the desiredcharacteristics and properties. The novel absorbable polymeric blends ofthe present invention will typically contain about 1.25 wt. % to about50 wt. % of the lower molecular weight component, more typically about12 wt. % to about 22 wt. %. The higher molecular weight component willtypically make up the remainder of the blends.

Table 1 describes parameters and ranges for the novel polymer blends ofthe present invention. Throughout this application, IV₁ refers to theinherent viscosity of blend component 1, IV₂ refers to the inherentviscosity of blend component 2, IV_(BLEND) refers to the inherentviscosity of the blend. Similarly, M_(w1) refers to the weight-averagemolecular weight of blend component 1, M_(w2) refers to theweight-average molecular weight of blend component 2, M_(wBLEND) refersto the weight-average molecular weight of the blend and M_(wFIBER)refers to the weight-average molecular weight of the fiber. Inherentviscosity measurements were made at a concentration of approximately 0.1g/dL at 25° C. in hexafluoroisopropanol (HFIP).

TABLE 1 Minimum Preferred Operating Factor Dimensions Value Range MaxValue IV₁ dL/g 0.9 1.4 to 1.7 2.5 Preferred: 1.45 to 1.55 IV₂ 0.1 0.20to 0.25 0.65 Preferred: 0.22 to 0.23 IV_(BLEND) 0.8 1.1 to 1.4 2 MostOften Observed: 1.15-1.25 IV_(FIBER) 0.5 0.90 to 1.05 1.8 Most OftenObserved: 0.95 to 1.0 M_(w1) Daltons 42,000 75,000 to 100,000 175,000Most Often Selected: 80,000 to 90,000 M_(w2) 1,400 4,700 to 5,200 24,000Most Often Selected: 4,800 to 5,000 M_(wBLEND) 35,000 55,000 to 75,000120,000 Most Often Observed: 58,000 to 65,000 M_(wFIBER) 18,000 40,000to 55,000 100,000 Most Often Observed: 42,000 to 46,000 Acid LevelsPercent 0.3 1.2 to 2.2 23, when blended Most Often 1.7 with a resin withan M_(w) of 80k Daltons⁽¹⁾ 28, when blended with a resin with an M_(w)of 120k Daltons⁽¹⁾ Weight Percent 1.25 12 to 22 Approximately Percent of(assuming an (using an 50 weight Low MW IR₂ of 5) IR₂ of 20) percent⁽¹⁾Component ⁽¹⁾Maximum acid levels depend on the particular application(suture, etc.), the M_(w) of the high molecular weight component, AND onthe value of IR₂ (2) Although IV_(FIBER), and M_(wFIBER) are listed inTABLE 1, these designators would apply to any medical device made fromthe inventive polymeric blends, not just fibers

In some instances, articles can be made directly from the blendcomponents by thermal processes; example of this include direct meltextrusion of a physical mixture of the blend components or directinjection molding of a physical mixture of the blend components. To beclear, a physical mixture of the blend components is introduced to thesupply hopper of the forming equipment, extruder, injection molder, etc.

Four individual blends of the subject invention were made and convertedinto yarns via multifilament extrusion, and orientation. The yarns werefurther processed into size 2/0 braids. The four blends were made tohave an acid level of 1.7 percent, similar to what is described in theExamples. The braids were coated to provide lubricity and a relevantamount of triclosan antibacterial agent; the coated braids weresterilized by ethylene oxide (EO).

Inherent viscosity measurements of the polymer blends and the tenacitiesof the yarns made therefrom, as well as molecular weight data ascollected from gel permeation chromatography (GPC) and IV measurementsmade on the corresponding braids are summarized in Tables 10 to 12.Throughout this application, M_(w) refers to the weight-averagemolecular weight, M_(n) refers to the number-average molecular weightand M_(z) refers to the z-average molecular weight.

The GPC samples were dissolved in hexafluoro-isopropanol (HFIP) atapproximately 2 mg/ml. After all the solid was dissolved, each solutionwas filtered by a 0.45 μm filter disk into a GPC vial for analysis. TheGPC/MALLS system used for the analysis comprised a Waters 2695 HPLC, aWyatt Optilab rEX Refractometer, and a Wyatt HELEOS II Multi-angle LaserLight Scattering Detector. Two PL HFIPgel columns (9 μm, 300 mm×7.5 mmi.d.) from Polymer Laboratories were used for separation. The columntemperature was set at 40° C. HFIP with 0.01M Lithium Bromide (LiBr)(0.2% v/v H2O) was used as the mobile phase and was delivered at aconstant flow rate of 0.7 ml/min. The injection volume was 70 μl. BothEmpower (Waters) and Astra (Wyatt) software were used for instrumentoperation and data analysis.

Molecular weight data as collected from GPC and inherent viscositymeasurements for the above braids after EO sterilization are shown belowin Table 12.

The polyglycolide homopolymer or the glycolide-rich glycolide/lactidecopolymer may be characterized by chemical analysis. Thesecharacteristics include, but are not limited to, an inherent viscosityrange from about 0.8 about 2 dL/g, as measured in hexafluoroisopropanol(HFIP) at 25° C. and at a concentration of 0.1 g/dL for resin of theinventive polymer blend. Gel permeation chromatography analysis showed aweight average molecular weight range from approximately 35,000 to120,000 Daltons. It is to be understood that higher molecular weightresins can be employed, provided the processing equipment used to formthe blend and to form the medical device are capable of handling themelt viscosities inherent to these higher molecular weights, and may bedesirable for certain applications. For example, in some applications, aresin with an inherent viscosity of 2.5 dL/g may be needed to producemedical devices requiring certain characteristics, such as higherstrength. The novel polymer blends of the present invention willtypically have a melting transition from approximately 185 to 224° C., aglass transition temperature range of about 35° C. to about 45° C., anda crystallinity level of about 30 to about 50 percent.

Nuclear magnetic resonance analysis confirmed that the driedco-polymeric resin is a random copolymer of glycolide and lactide. It isto be understood that different isomers of lactide can be used, such asL(−)-lactide or D(+)-lactide or meso-lactide.

The characteristics of the polymer blends of the present invention willbe sufficiently effective to provide the needed physical properties toallow the surgical devices to function as intended, yet lose thesemechanical properties at a rate much quicker than convention syntheticabsorbable polymers of like composition.

For the purpose of this application we wish to define the term ofcapping or end-capping. Capping or end-capping is the chemicalmodification of the polymer chain termini. These terms also refer to thechemical modification of the chain termini of low molecular weightpolymers or oligomers. For clarification purposes let us considerring-opening polymerization where one starts with an initiator andlactone monomers. Let us first consider a monofunctional alcoholinitiator such as 1-dodecanol. In this case the resulting polymer chainshave an alkyl functionality on one end and an alcoholic functionality onthe other. One can now chemically modify the alcoholic functionalityinto a carboxylic functionality. This can be conveniently accomplishedby reaction of the alcohol chain end with a cyclic anhydride, such asdiglycolic anhydride or succinic anhydride. For the purposes of thisapplication we can describe this polymer to be end-capped with acarboxylic acid functionality.

Similarly, one could consider using an initiator containing both acarboxylic acid functionality and an alcohol group, such as glycolicacid. In this case the resulting polymer chains have a carboxylic acidfunctionality on one end and an alcoholic functionality on the other.One can now again chemically modify the alcoholic functionality into acarboxylic acid functionality. For the purposes of this application wecan describe this polymer to be end-capped with a carboxylic acidfunctionality. To be clear, we do not consider the glycolic acidinitiated polymer to be end-capped until its end is converted into acarboxylic acid, for example by further reaction with a cyclicanhydride.

Finally, one could consider using an initiator containing two alcoholfunctionalities, such as diethylene glycol. In this case the resultingpolymer chains have alcoholic functionalities on both ends. One can nowchemically modify both alcoholic functionalities into carboxylic acidfunctionalities. For the purposes of this application we can describethe latter two polymers to be end-capped with a carboxylic acidfunctionality.

It should be clear to those having ordinary skill in the art that thecapping can be achieved in multiple ways. These could include also forexample direct oxidation of the chain ends.

In one embodiment of the present invention, the percentage ofend-capping of the novel absorbable polymer blend with carboxylic acidgroups is at least 25 percent. In another embodiment of the presentinvention, the percentage of end-capping of the novel absorbable polymerblend with carboxylic acid groups for the first polymeric component isfrom about 0 to about 100%, and the percentage of end-capping withcarboxylic acid groups for the second polymeric component is from about25% to about 100%.

In one embodiment of the present invention the polymer blend contains aconventional dye. The dye should be one acceptable for clinical use;this includes, without limitation, D&C Violet No. 2 and D&C Blue No. 6and similar combinations thereof. It should be noted that one or more ofthe blend components may be dyed or the dye can be introduced during theblend compounding stage. Additionally, in another embodiment, onepolymeric component of the blend might be colored with a first dye at agiven concentration, and the second polymeric component colored with thesame or another dye at the same or another concentration.

The novel polymer blends of the present invention can be manufacturedfrom the individual components using a variety of conventional processesusing conventional processing equipment. Examples of manufacturingprocesses include chemical reactions of the ring-opening andpolycondensation type, devolatilization and resin drying, dry blendingin a tumble dryer, solution blending, extrusion melt-blending, injectionmolding, thermal annealing, and ethylene oxide sterilization processes.An alternate to dry blending with subsequent melt blending of themixture may include the use of two or more conventional feeders,preferably loss-in-weight feeders, that supply the components to beblended to an extruder; the extruder can be of the single screw or twinscrew variety.

Alternately, multiple extruders can be used to feed melts of the blendcomponents, such as in co-extrusion. The novel polymer blends of thepresent invention may be made using conventional thermal processes.Examples of thermal processes to produce the polymer blends of thepresent invention include melt blending in an extruder, which caninclude twin screw blending or single screw extrusion, co-extrusion,twin screw blending with simultaneous vented-screw vacuumdevolatilization, vacuum tumble drying with thermal devolatilization,monomer removal by solvent extraction at elevated temperature, and resinannealing.

The polymer components, as well as blends of the subject invention canbe sized by conventional means such as pelletization, granulation, andgrinding.

A further embodiment of the present invention would be feedingappropriately sized particles of the blend components directly to thehopper of the extruder or the injection molding machine. It would bepossible for one skilled in the art to apply this technique to otherprocessing methodologies, such as, but not limited to, film or fiberextrusion. Limiting the thermal history of the polymer blend componentsis advantageous in that it avoids the possibility of prematuredegradation. Additional methods of thermal processing can include aprocess selected from the group consisting of injection molding,compression molding, blow molding, blown film, thermoforming, filmextrusion, fiber extrusion, sheet extrusion, profile extrusion, meltblown nonwoven extrusion, co-extrusion, tube extrusion, foaming,rotomolding, calendaring, and extrusion. As noted earlier, appropriatelysized particles of the blend components can be blended in the melt usingthese thermal processing means. In some cases it may be possible anddesirable to use solution processing techniques, such as solutionspinning, gel spinning and electro spinning.

Other examples of conventional manufacturing process equipment that maybe used to manufacture the novel polymer blends of the present inventionmay include single-screw and twin-screw compounders that operate on acontinuous basis or batch-style compounders.

The equipment will be sufficiently sized to effectively and provide thedesired batch size. Examples of such equipment include chemical reactorsranging in size, for example, from two-gallon to seventy-five gallon ormore in capacity, process devolatilization dryers ranging, for example,from one cubic feet to twenty cubic feet or more, single and twin-screwextruders ranging, for example, from about one inch to about threeinches in diameter, and injection molders ranging, for example, fromabout seven to about 40 tons or more in size. A preferred method andassociated equipment for manufacturing the polymer blends of the presentinvention can be found in Examples 7 to 9.

If desired, the polymer blends of the present invention may containother conventional components and agents. The other components,additives or agents will be present to provide additional desiredcharacteristics to the polymer blends and medical devices of the presentinvention including antimicrobial characteristics, controlled drugelution, radio-opacification, and enhanced osseointegration.

Such other components will be present in a sufficient amount toeffectively provide for the desired effects or characteristics.Typically, the amount of the other adjuncts will be about 0.1 weightpercent to about 20 weight percent, more typically about 1 weightpercent to about 10 weight percent and preferably about 2 weight percentto about 5 weight percent based on the total weight of the blend.

The variety of therapeutic agents that can be used in the polymer blendsof the present invention is vast. In general, therapeutic agents whichmay be administered via compositions of the invention include, withoutlimitation, antiinfectives, such as antibiotics and antiviral agents.

Such other components will be present in a sufficient amount toeffectively provide for the desired effects or characteristics.Typically, the amount of the other adjuncts will be about 0.1 weightpercent to about 20 weight percent, more typically about 1 weightpercent to about 10 weight percent and preferably about 2 weight percentto about 5 weight percent.

Examples of antimicrobial agents include the polychloro phenoxy phenolssuch as 5-chloro-2-(2,4-dichlorophenoxy)phenol (also known asTriclosan). Examples of radio-opacification agents include bariumsulfate while examples of osseointegration agents include tricalciumphosphate.

The variety of therapeutic agents that can be used in the polymer blendsof the present invention is vast. In general, therapeutic agents whichmay be administered via pharmaceutical compositions of the inventioninclude, without limitation, antiinfectives, such as antibiotics andantiviral agents; analgesics and analgesic combinations; anorexics;antihelmintics; antiarthritics; antiasthmatic agents; adhesionpreventatives; anticonvulsants; antidepressants; antidiuretic agents;antidiarrheals; antihistamines; anti-inflammatory agents; antimigrainepreparations; contraceptives; antinauseants; antineoplastics;antiparkinsonism drugs; antipruritics; antipsychotics; antipyretics,antispasmodics; anticholinergics; sympathomimetics; xanthinederivatives; cardiovascular preparations including calcium channelblockers and beta-blockers such as pindolol and antiarrhythmics;antihypertensives; diuretics; vasodilators, including general coronary,peripheral and cerebral; central nervous system stimulants; cough andcold preparations, including decongestants; hormones, such as estradioland other steroids, including corticosteroids; hypnotics;immunosuppressives; muscle relaxants; parasympatholytics;psychostimulants; sedatives; tranquilizers; naturally derived orgenetically engineered proteins, polysaccharides, glycoproteins, orlipoproteins; oligonucleotides, antibodies, antigens, cholinergics,chemotherapeutics, hemostatics, clot dissolving agents, radioactiveagents and cystostatics. Therapeutically effective dosages may bedetermined by in vitro or in vivo methods. For each particular additive,individual determinations may be made to determine the optimal dosagerequired. The determination of effective dosage levels to achieve thedesired result will be within the realm of one skilled in the art. Therelease rate of the additives may also be varied within the realm of oneskilled in the art to determine an advantageous profile, depending onthe therapeutic conditions to be treated.

Suitable glasses or ceramics include, but are not limited to phosphatessuch as hydroxyapatite, substituted apatites, tetracalcium phosphate,alpha- and beta-tricalcium phosphate, octacalcium phosphate, brushite,monetite, metaphosphates, pyrophosphates, phosphate glasses, carbonates,sulfates and oxides of calcium and magnesium, and combinations thereof.

The novel absorbable medical devices of the present invention that aremade from the novel absorbable polymer blends of the present inventioninclude, but are not limited to, conventional medical devices,especially fibrous devices such as monofilament-based andmultifilament-based sutures and meshes, woven fabrics, nonwoven fabrics,knitted fabrics, fibrous bundles, cords, and other implantable medicaldevices, including staples, tacks, clips, tissue fixation devices, meshfixation devices, anastomotic devices, suture anchors and bone anchors,tissue and bone screws, bone plates, prostheses, support structures,tissue augmentation devices, tissue ligating devices, patches,substrates, tissue engineering scaffolds, composites, bone grafts, drugdelivery devices, stents, bone waxes and bone fillers, combinations andequivalents.

Referring to FIGS. 1A-D, illustrations of conventional braided surgicalsutures that can be made from the novel absorbable polymer blends of thepresent invention are seen. The sutures are seen to be made or braidedfrom filaments or multifilament yarns, and the sutures may have a coreconstruction. An illustration of a conventional monofilament suture thatcan be made from the novel absorbable polymer blends of the presentinvention alongside of a conventional surgical needle is seen in FIG. 2.A surgical tack that can be molded from the novel absorbable polymerblends of the present invention is illustrated in FIG. 3.

For purposes of this application, we wish to use the term suture to meansurgical sutures, and more broadly fibrous devices, includingmonofilament and multifilament yarns used in the medical field. Theseinclude, but are not limited to, fibers used to make surgical meshes;fibers used to make surgical fabrics and tapes made by any known methodof processing (knitted, woven, nonwoven, etc). The sutures of thepresent invention may be used for a variety of applications including,but not limited to wound fixation, wound closure, general tissueapproximation, and attachment of implants.

Modern surgical sutures generally range from Size 5 (heavy braidedsuture for orthopedics) to Size 11/0 (for example, a fine monofilamentsuture for ophthalmics). The actual diameter of thread for a givenU.S.P. size differs depending on the suture material class. Thediameters of sutures in the synthetic absorbable suture class are listedin the United States Pharmacopeia (USP) as well as in the EuropeanPharmacopoeia. The USP standard is more commonly used.

We have found that the polymeric blends of the present invention may beused to produce sterile surgical sutures possessing significant initialbreaking strength, which then possess little or no mechanical strengthafter 14 days post-implantation, and absorb in about 42 dayspost-implantation. These inventive sutures of a given size (diameter)possess as much initial breaking strength as a suture one size larger ofpresently available sterile, fast-absorbing, commercial sutures thatlose most of their breaking strength at 14 days post-implantation andare substantially absorbed in about 42 days.

The polymeric components of the medical devices of the present inventionwill have an inherent viscosity of at least about 0.5 dL/g as measuredin hexafluoroisopropanol at 25° C. at a concentration of 0.1 g/dL,provided the medical device is fully soluble in this solvent.

Injection Molding

Injection molding is a process well-known in the plastic industry. It isdesigned to produce parts of various shapes and sizes by melting theplastic, mixing and then injecting the molten resin into a suitablyshaped mold. After the resin is solidified, the part is generallyejected from the mold and the process continued.

For the purposes of this invention, a conventional 30-ton electricallycontrolled injection molding machine can be used. The polymer blends ofthe present invention can be processed in the following general manner.The polymer and polymer blends can be fed by gravity from a hopper,under nitrogen purge, into a heated barrel. The polymer will generallymove forward in the barrel by the screw-type plunger into a heatedchamber. As the screw advanced forward, the molten polymer and polymerblends will be forced through a nozzle that rests against a mold,allowing the polymer and polymer blends to enter a specially designedmold cavity, through a gate and runner system. The blend will be formedinto the part in the mold cavity, and then allowed to cool at a giventemperature for a period of time. It will be then removed from the mold,or ejected, and separated from the gate and runner.

A further aspect of the present inventive polymer blends is thepersistence of weight-average molecular weight upon thermal processing.A benefit of having the weight-average molecular weight not change muchduring thermal processing, such as melt extrusion, is the enabling ofhigher mechanical properties in the fabricated devices so produced. Wehave found that in the case of producing multifilament yarns, a minimumweight-average molecular weight of about 35,000 Daltons in the yarns isdesirable. If the weight-average molecular weight of the polymer blenddrops too much during thermal processing, it would be difficult toachieve a minimum weight-average molecular weight in the resultingmedical device, and hence, allowing the part to possess the minimumdesired mechanical properties.

An additional further aspect of the present inventive absorbable polymerblends is the incorporation of a third polymeric component, wherein saidthird polymeric component is selected from the group consisting ofnon-absorbable polymers, rapidly absorbing polymers, and slowlyabsorbing polymers.

It is to be noted that the present inventive polymeric blends allow forthe manufacture of inventive medical devices that can comprise anantimicrobial agent such as triclosan. Of particular interest aresurgical sutures treated with this antimicrobial agent. Presentlyavailable sterile, fast-absorbing, commercial sutures that lose most oftheir breaking strength at 14 days post-implantation and aresubstantially absorbed in about 42 days are not treated with triclosan.Attempts to produce such a suture comprising triclosan are fraught withprocessing difficulties. Using the inventive polymer blends describedherein, we have been able to produce sterile surgical sutures treatedwith triclosan that lose most of their breaking strength at 14 dayspost-implantation and are substantially absorbed in about 42 days.

Another aspect of the present invention is a suture having an absorptiontime at least 20% shorter than the absorption time of a similar sutureconsisting essentially of the first polymeric component. Yet anotheraspect is a suture having a post-implantation time required to achievezero mechanical strength at least 30% shorter than the post-implantationtime required to achieve zero mechanical strength for a similar sutureconsisting essentially of the first polymeric component. Yet anotheraspect is a suture having a pre-implantation strength greater than orequal to 75% of the pre-implantation strength of a similar sutureconsisting essentially of the first polymeric component.

The following examples are illustrative of the principles and practiceof the present invention, although not limited thereto.

Example 1

Synthesis of Uncapped, Dodecanol Initiated at IR 800, 16 PPM Tin, 90/10Poly(L(−)-Lactide-Co-Glycolide)

Into a suitable 50-gallon stainless steel oil jacketed reactor equippedwith agitation, 24.66 kg of L(−)-lactide and 175.34 kg of glycolide wereadded along with 391.89 g of dodecanol and 74.24 g of a 0.33M solutionof stannous octoate in toluene. The reactor was closed and a purgingcycle, along with agitation at a rotational speed of 13 RPM in an upwarddirection, was initiated. The reactor was evacuated to pressures lessthan 2 Torr, and was held at this condition for at least 15 minutes,followed by the introduction of nitrogen gas. The vacuum-nitrogen purgecycle was repeated once more to ensure a dry atmosphere.

At the end of the final introduction of nitrogen, the pressure wasadjusted to be slightly above one atmosphere. The heating oiltemperature was raised to 135° C. When the batch temperature reached120° C., the agitator was stopped and restarted in the downwarddirection at 13 rpm.

The vessel was heated by computer control at a various rates, dependingon the batch temperature and the temperature difference between the oiljacket and batch, T₀−T_(B).

For the batch temperature interval from room temperature up to 199° C.,for T₀−T_(B) equal or smaller than 3° C., the heating rate was 42° C.per hour, and for T₀−T_(B) greater than 3° C., the heating rate was 24°C. per hour. When the batch temperature reached 170° C., the agitatorspeed was reduced to 6 RPM. When the batch molten mass reached 200° C.the reaction continued for an additional 100 minutes. The oiltemperature was ramped up at an average rate of 30° C. per hour andremained at 199-205° C.

At the end of the reaction period, the oil temperature was increased to212° C., and the polymer was discharged from the vessel, by means of apolymer melt pump, into an underwater pelletizer. During pelletization,the pelletized polymer was transferred to a centrifugal dryer whereoversized material was separated at the agglomerate catcher chute. Thepelletization cutter speed was adjusted to give an average pellet weightof 25 mg.

The polymer pellets were transferred to a 20 cubic foot stainless steelrotary vacuum dryer. The dryer was closed and the pressure was reducedto less than 200 mTorr. Once the pressure was below 200 mTorr, tumblerrotation was activated at a rotational speed of 6 RPM and the batch wasvacuum conditioned for a period of 18 hours. After the 18 hour vacuumconditioning, the oil temperature was set to a temperature of 110° C.,for a period of 24 hours. At the end of this heating period, the batchwas allowed to cool for a period of at least 4 hours, while maintainingrotation and high vacuum. The polymer was discharged from the dryer bypressurizing the vessel with nitrogen, opening the slide-gate, andallowing the polymer granules to descend into waiting vessels for longterm storage.

The long term storage vessels were air tight and outfitted with valvesallowing for evacuation so that the resin is stored under vacuum. Theresin was characterized. It exhibited an inherent viscosity of 1.53dL/g, as measured in hexafluoroisopropanol at 25° C. and at aconcentration of 0.10 g/dL. Gel permeation chromatography analysisshowed a weight average molecular weight of approximately 82,600Daltons. Differential scanning calorimetry revealed a glass transitiontemperature of 45° C. and a melting transition at 197° C. Nuclearmagnetic resonance analysis confirmed that the resin was a randomcopolymer of polymerized L(−)-lactide and glycolide. X-ray diffractionanalysis showed a crystallinity level of approximately 37.6 percent.

Example 2

In a manner similar to Example 1, a synthesis was conducted to preparean dodecanol initiated, 90/10 poly(L(−)-lactide-co-glycolide) copolymer.It exhibited a similar inherent viscosity as the copolymer of Example 1.The copolymer of this Example 2 was converted into an inventive polymerblend, which was then subsequently extruded and processed into braidedsuture materials, which were then utilized for in vivo testing.

Example 3

Synthesis of Capped, IR 600, 6.6 PPM Tin, 90/10Poly(L(−)-Lactide-Co-Glycolide)

Into a suitable 10-gallon stainless steel oil jacketed reactor equippedwith agitation, 3.080 kg of L(−)-lactide and 21.919 kg of glycolide wereadded along with 26.64 g of glycolic acid and 4.25 ml of a 0.33Msolution of stannous octoate in toluene. The reactor was closed and apurging cycle, along with agitation at a rotational speed of 7 RPM in anupward direction, was initiated. The reactor was evacuated to pressuresless than 200 mTorr, and was held at this condition for at least 15minutes, followed by the introduction of nitrogen gas. The cycle wasrepeated two times to ensure a dry atmosphere.

At the end of the final introduction of nitrogen, the pressure wasadjusted to be slightly above one atmosphere. The heating oiltemperature was raised to 130° C. at an average heating rate of 120°C./hour. When the batch temperature reached 120° C., the agitator wasstopped and restarted in the downward direction at 7 rpm.

The heating oil controller was set at 203° C. at an average heating rateof 60° C. per hour. When the batch molten mass reached 200° C., thereaction was continued for an additional 5 hours at 7 RPM.

The agitator was stopped and the reactor was placed under a slightnitrogen purge with open venting. The charging port was opened and 40.66grams of diglycolic anhydride was added to the reaction mass. Thereactor port was closed. Venting and nitrogen purging were stopped.Agitation was resumed at 7 rpm and the reaction was continued for anadditional hour at an average oil heating temperature of 202° C.

At the end of the reaction period, the polymer was discharged from thevessel into aluminum trays and was stored in a freezer. The polymer wasground and was screened through a 3/16″ screen, and it was dried in athree cubic foot rotary vacuum dryer, at 10 rpm for 18 hours, at roomtemperature. At the end of the period the vacuum was 50 mTorr, thedrying cycle continued for an additional 19 hours under vacuum at 110°C. At the end of this heating period, the batch was allowed to cool fora period of at least 4 hours, while maintaining rotation and highvacuum. The polymer was discharged from the dryer by pressurizing thevessel with nitrogen, opening the slide-gate, and allowing the polymergranules to descend into waiting vessels for long term storage. Theresin was characterized. Gel permeation chromatography analysis showed aweight average molecular weight of approximately 65,500 Daltons.Differential scanning calorimetry revealed a glass transitiontemperature of 39° C. and a melting transition at 201° C. Nuclearmagnetic resonance analysis confirmed that the resin was a randomcopolymer of polymerized L(−)-lactide and glycolide.

Example 4

Synthesis of Dodecanol Initiated, Uncapped, IR 20, 6.6 PPM Tin, 10/90Oligo(L(−)-Lactide-Co-Glycolide)

Into a suitable 2 gallon stainless steel oil jacketed reactor equippedwith agitation, 862.58 grams of L(−)-lactide and 6137.42 grams ofglycolide were added along with 548.35 g of dodecanol and 1.19 ml of a0.33M solution of stannous octoate in toluene. The reactor was closedand a purging cycle, along with agitation at a rotational speed of 7 RPMin an upward direction, was initiated. The reactor was evacuated topressures less than 220 mTorr, and was held at this condition for atleast 15 minutes, followed by the introduction of nitrogen gas. Thecycle was repeated once again to ensure a dry atmosphere.

At the end of the final introduction of nitrogen, the pressure wasadjusted to be slightly above one atmosphere. The heating oiltemperature was raised to 130° C. at an average heating rate of 228°C./hour. When the batch temperature reached 120° C., the agitator wasstopped and restarted in the downward direction at 7 RPM.

The heating oil controller was set at 203° C. at an average heating rateof 60° C. per hour. When the batch molten mass reached 200° C. thereaction continued for an additional 2 hours and 25 minutes at 7 rpm.The heating oil controller was set at 205° C. and the reaction continuedfor an additional 2 hours and 15 minutes.

At the end of the reaction period, the polymer was discharged from thevessel into aluminum trays and was stored in a freezer. The polymer wasground and was screened through a 3/16″ screen, and it was stored undervacuum. The resin was characterized.

Gel permeation chromatography analysis showed a weight average molecularweight of approximately 4,550 Daltons and a number average molecularweight of 2,620 Daltons. Differential scanning calorimetry revealed aglass transition temperature of 39° C. and a melting transition at 183°C. for this semi-crystalline polymer. Since the initiator employed inthis polymerization did not contain a carboxylic acid group and theresulting reaction product was not end-capped, the expected acid levelfor this polymer is expected to be close to zero.

Example 5

Synthesis of Capped, IR 20, 6.6 PPM Tin, 10/90Oligo(L(−)-Lactide-Co-Glycolide)

Into a suitable 2 gallon stainless steel oil jacketed reactor equippedwith agitation, 862.58 grams of L(−)-lactide and 6,137.4 grams ofglycolide were added along with 223.8 g of glycolic acid and 1.19 ml ofa 0.33M solution of stannous octoate in toluene. The reactor was closedand a purging cycle, along with agitation at a rotational speed of 7 RPMin an upward direction, was initiated. The reactor was evacuated topressures less than 200 mTorr, and was held at this condition for atleast 15 minutes, followed by the introduction of nitrogen gas. Thecycle was repeated once again to ensure a dry atmosphere.

At the end of the final introduction of nitrogen, the pressure wasadjusted to be slightly above one atmosphere. The heating oiltemperature was raised to 130° C. at an average heating rate of 120°C./hour. When the batch temperature reached 120° C., the agitator wasstopped and restarted in the downward direction at 7 RPM.

The heating oil controller was set at 203° C. at an average heating rateof 60° C. per hour. When the batch molten mass reached 200° C., thereaction was continued for an additional 4 hours and 25 minutes at 7RPM. The agitator was stopped and 341.58 grams of diglycolic anhydridewas added to the reactor. Agitation was continued for 60 minutes at 10RPM in the downward direction.

At the end of the reaction period, the polymer was discharged from thevessel into aluminum trays and was stored in a freezer. The polymer wasground and was screened through a 3/16″ screen, and it was stored undervacuum. The resin was characterized. It exhibited an inherent viscosityof 0.25 dL/g, as measured in hexafluoroisopropanol at 25° C. and at aconcentration of 0.10 g/dL. Gel permeation chromatography analysisshowed a weight average molecular weight of approximately 5,390 Daltons.Differential scanning calorimetry revealed a glass transitiontemperature of 34° C. and a melting transition at 197° C.

Nuclear magnetic resonance analysis confirmed that the resin was arandom copolymer of polymerized L(−)-lactide and glycolide, with acomposition of 7.7 percent polymerized L(−)-lactide, 87 percentpolymerized glycolide, 0.1 percent lactide monomer, and 0.6 percentglycolide monomer, and 3.0 percent acid groups resulting fromend-capping, as measured on a molar basis. X-ray diffraction analysisshowed a crystallinity level of approximately 54.5 percent.

Example 6

Synthesis of Capped, IR 20, 6.6 PPM Tin, 10/90Oligo(L(−)-Lactide-Co-Glycolide)

In a manner similar to Example 5, a synthesis was conducted to preparean glycolic acid initiated, 90/10 oligo(L(−)-lactide-co-glycolide)co-oligomer. The resin was characterized; it exhibited an inherentviscosity of 0.25 dL/g, as measured in hexafluoroisopropanol at 25° C.and at a concentration of 0.10 g/dL. Gel permeation chromatographyanalysis showed a weight average molecular weight of approximately 4,870Daltons and a number average molecular weight of 2,990 Daltons.

Nuclear magnetic resonance analysis confirmed that the resin was arandom copolymer of polymerized L(−)-lactide and glycolide, with acomposition of 6.8 percent polymerized L(−)-lactide, 85.9 percentpolymerized glycolide, 0.4 percent lactide monomer, and 1.0 percentglycolide monomer, and 4.1 mole percent acid groups resulting from thecapping step.

Example 7

Dry Blending, Melt Blending, Pelletizing and Drying of Pellets

The Processing of a Mixture of the Polymer of Example 1 and the Polymerof Example 5 Resulting in a Blend

Dry Blending of the Blend Components

Once the glycolide/lactide polymers had been produced by the abovedescribed methods in the previous examples, appropriate amounts of thesecomponents, in divided form (pellets in Example 1 and ground polymer inExample 5) were combined in a dry blend. These dry blends are producedon a weight basis, depending on the particular application and surgicalneed. In the present Example, uncapped, dodecanol-initiated at IR 800,16 PPM tin, 10/90 poly(L(−)-lactide-co-glycolide) at 83 weight percentand the lower molecular weight capped, IR 20, 6.6 PPM tin, 10/90poly(L(−)-lactide-co-glycolide) of Example 5 at 17 weight percent, weredry blended as described below. This lower molecular weight resin canalso be referred to as oligo(L(−)-lactide-co-glycolide).

Into a clean 3-cubic foot Patterson-Kelley dryer, 12.210 kilograms ofthe pelletized glycolide/lactide copolymer of Example 1 were added,followed by 2.501 kilograms of the polymer granules of Example 5. Thedryer was closed, and the vessel pressure was reduced to less than 200mTorr. The dryer rotation was started at 10 RPM and continued for aminimum period of one hour. The dry blend was then discharged intoportable vacuum storage containers, and these containers were placedunder vacuum, until ready for the melt blending step. (Note that meltblending is often described as polymer compounding.)

For the purpose of this invention, blends of this type can be producedin a similar manner with different compositions.

Melt Blending (Compounding) and Pelletization

Once the dry blends have been produced and have been vacuum conditionedfor at least three days to insure low moisture content, themelt-blending step can begin. A Werner & Pfeidlerer Twin-Screw Extruder,Model ZSK-30, was fitted with screws designed for melt blending,utilizing a vacuum port for purposes of volatilizing residual monomer.The screw design contained several different types of elements,including conveying, compression, mixing and sealing elements. Theextruder was fitted with a three-hole die plate. A chilled water bathwith water temperature set between 40 and 70° F. was placed near theextruder outlet. A strand pelletizer and pellet classifier was placed atthe end of the water bath. The extruder temperature zones were heated toa temperature of 190 to 210° C., and the vacuum cold traps were set to−20° C. The pre-conditioned dry blend granules were removed from vacuumand placed in a twin-screw feed hopper under nitrogen purge. Theextruder screws were set to a speed of 225 RPM, and the feeder wasturned on, allowing the dry blend to be fed into the extruder at a rateof approximately 0.230 kilograms/minute. Throughput could be adjusted byadjusting the feeder rate as is well known. A feed rate is selectedbased on a balance of economy and degradation avoidance.

The polymer melt blend was allowed to purge through the extruder untilthe feed was consistent, at which point the vacuum was applied to thevacuum port. The polymer blend extrudate strands were fed through thewater bath and into the strand pelletizer. The pelletizer cut thestrands into appropriate sized pellets; specifically, with a diameter ofabout 2 mm and an approximate length of 3 mm. The pellets were then fedinto the classifier. The classifier separated larger and smaller pelletsfrom the desired size, usually a weight of about 13 mg per pellet. Thisprocess continued until the entire polymer dry blend was melt blended inthe extruder, and formed into substantially uniform pellets. The pelletproduction rate was approximately 170 grams per minute. Samples weretaken throughout the extrusion process and were measured for polymercharacteristics such as inherent viscosity, molecular weight andcomposition. Once the melt-blending process was completed, the weighed,pelletized polymer was placed into a dryer as described below.Alternately, if the drier is not immediately available, the pellets maybe placed in polyethylene bags, weighed, and stored in a freezer below−20° C. to await devolatilization of residual monomer.

Drying of Pellets

The polymer melt-blend was placed into a 3-cubic foot Patterson-Kelleydryer, which was placed under vacuum. The dryer was closed and thepressure was reduced to less than 200 mTorr. Once the pressure was below200 mTorr, dryer rotation was activated at a rotational speed of 10 RPMwith no heat for 6 hours. After the 6 hour period, the oil temperaturewas set to 110° C. The oil temperature was maintained at 110° C. for aperiod of 12 hours. At the end of this heating period, the batch wasallowed to cool for a period of at least 4 hours, while maintainingrotation and vacuum. The polymer melt-blend pellets were discharged fromthe dryer by pressurizing the vessel with nitrogen, opening thedischarge valve, and allowing the polymer pellets to descend intowaiting vessels for long term storage. The storage vessels were airtight and outfitted with valves allowing for evacuation so that theresin was storage under vacuum. The resin was characterized. GelPermeation chromatography analysis revealed a weight average molecularweight of 58,300 Daltons. Differential thermal analysis showed a glasstransition temperature, T_(g) of 46° C. and a melting point of 198° C.

For the purpose of this invention, blends of this type with differentcompositions can be produced in a similar manner.

Example 8

Dry-Blending, Melt-Blending, Pelletization and Drying of a ComparativeExample (Blend of Example 1 and Example 4; 0% Acid)

Dry-Blending

In a manner analogous to Example 7, a dry blend containing 83 weightpercent of uncapped, Dodecanol Initiated at IR 800, 16 PPM Tin, 90/10Poly(glycolide-co-L(−)-lactide) as described in Example 1, and uncapped,IR 20, 6.6 PPM Tin, 90/10 Poly(glycolide-co-L(−)-lactide) as describedin Example 4, at 17 weight percent, was dry blended in a clean 3-cubicfoot commercially available Patterson-Kelley dryer; 5,000 grams ofpellets of the glycolide/lactide copolymer of Example 1 were weighed andadded to the dryer. In the same 3-cubic foot dryer, 1024 grams ofpolymer granules of Example 4 were weighed and added to the dryer. Thedryer was closed, and the vessel pressure was reduced to less than 200mTorr. The rotation was started at 10 RPM and continued for a minimumperiod of one hour. The dry blend was then discharged into portablevacuum storage containers, and these containers were placed undervacuum, until ready for the next step.

Melt-Blending (Compounding) and Pelletization

Once the dry blends have been produced and have been vacuum conditionedfor at least three days, the melt-blending step can begin. Acommercially available ZSK-30 twin-screw extruder was fitted with screwsdesigned for melt blending utilizing a vacuum port for purposes ofvolatilizing residual monomer. The screw design contained severaldifferent types of elements, including conveying, compression, mixingand sealing elements. The extruder was fitted with a three-hole dieplate, and a chilled water bath with water temperature set between 40and 70° F. was placed near the extruder outlet. A strand pelletizer andpellet classifier was placed at the end of the water bath. The extrudertemperature zones were heated to a temperature of 190 to 210° C., andthe vacuum cold traps were set to −20° C. The pre-conditioned dry blendgranules were removed from vacuum and placed in a twin-screw feed hopperunder nitrogen purge. The extruder screws were set to a speed of 225RPM, and the feeder was turned on, allowing the dry blend to be fed intothe extruder.

The polymer melt blend was allowed to purge through the extruder untilthe feed was consistent, at which point the vacuum was applied to thevacuum port. The polymer blend extrudate strands were fed through thewater bath and into the strand pelletizer. The pelletizer cut thestrands into appropriate sized pellets. The pellets were then fed intothe classifier and were measured for polymer characteristics such asinherent viscosity, molecular weight and composition. Once themelt-blending process was completed, the pelletized polymer was placedin polyethylene bags, weighed, and stored in a freezer below −20° C. toawait devolatilization of residual monomer. Samples of the undriedpellets were taken at the start and towards the end of the pelletizingoperation were analyzed by gel permeation chromatography revealingconsiderably lower weight average molecular weights than in theinventive example. GPC and revealed a weight average molecular weight of38,500 Daltons at the start of the pelletization and 36,800 Daltonstowards the end.

Drying of Pellets

The polymer melt-blend was placed into a 3-cubic foot Patterson-Kelleydryer, which was placed under vacuum. The dryer was closed and thepressure was reduced to less than 200 mTorr. Once the pressure was below200 mTorr, dryer rotation was activated at a rotational speed of 12 RPMwith no heat for 6 hours. After the 6 hour period, the oil temperaturewas set to 110° C. The oil temperature was maintained at 110° C. for aperiod of 12 hours. At the end of this heating period, the batch wasallowed to cool for a period of at least 4 hours, while maintainingrotation and vacuum. The polymer melt-blend pellets were discharged fromthe dryer by pressurizing the vessel with nitrogen, opening thedischarge valve, and allowing the polymer pellets to descend intowaiting vessels for long term storage. The storage vessels were airtight and outfitted with valves allowing for evacuation so that theresin was storage under vacuum. The resin was characterized. GelPermeation chromatography analysis revealed a weight average molecularweight of 40,300 Daltons and a number average molecular weight of 15,200Daltons. Differential thermal analysis showed a glass transitiontemperature, T_(g) of 38° C. and a melting point of 199° C.

Example 9

Dry-Blending, Melt-Blending, Pelletization and Drying of a ComparativeExample (Blend of Example 6 and Example 2; 1.7% Acid)

In a manner analogous to Example 7, pellets were prepared starting witha blend of 83 weight percent of the uncapped 90/10poly(glycolide-co-L(−)-lactide) copolymer of Example 2, and capped 90/10oligo(glycolide-co-L(−)-lactide) oligomer of Example 6, at 17 weightpercent. Melt Blending Molecular Weight Data with times is presented inTable 2.

TABLE 2 Melt Blending Molecular Weight Data M_(w) M_(n) M_(z) Sample(10³ g/mol) (10³ g/mol) (10³ g/mol) M_(w)/M_(n) At the Start (14:00)Injection 1 64.6 16.8 125.1 3.85 Injection 2 63.6 18.4 122.5 3.45Injection 3 64.0 17.1 125.5 3.75 Average Values 64.1 17.4 124.4 3.68 Inthe “Middle” (14:30) Injection 1 62.4 18.1 119.8 3.44 Injection 2 63.817.3 124.1 3.68 Injection 3 62.2 17.3 122.3 3.60 Average Values 62.817.6 122.1 3.57 At the End (15:10) Injection 1 64.7 15.8 128.3 4.09Injection 2 64.2 17.3 126.0 3.72 Injection 3 64.0 16.7 127.1 3.83Average Values 64.3 16.6 127.1 3.88 After Drying Injection 1 62.7 16.3125.0 3.86 Injection 2 64.8 17.2 123.3 3.78 Average Values 63.8 16.7124.2 3.82

Example 10

Extrusion and Orientation of the Pellets of Example 7

The polymer melt-blend described in Example 7 was used to producefilaments and, thereafter, bio-absorbable multifilament braided sutures.Except for the various temperatures the extruder apparatus and theprocess conditions were substantially the same for all describedexamples. For example, the spinneret had capillaries of 300 μm indiameter and L/D ratio of 7/1.

The take-up speed for the as-spun filaments was fixed at 1730 feet perminute. The drawing conditions for the examples consisted of a feed rollspeed of about 58.8 meters per minute, and a series of other rollersrunning at speeds corresponding to the following draw ratios: 1.008,5.000, 1.030, 1.00. This results in an overall (total) draw of 5.191;the collection speed was 305 meters per minute. The roller temperaturesfor each of the rolls in consecutive order were: 65 to 71° C. (RollerA), 75 to 100° C. (Roller B), 85 to 105° C. (Roller C), and ambient.

Table 3 below, provides the data for the extrusion and orientationconditions for Examples 10, 11 and 12 including die temperatures andorientation roll temperatures.

Table 4 further below, provides the data for the characteristics of theresulting multifilament yarns for this Example 10 and Example 12,including the tenacity, and the elongation-to-break. Small variations inthe basic processing conditions resulted in three separate extrudatelots. The oriented yarn mechanical properties results for Example 11 andExample 12 are included in Table 4 as well. The number of filaments foreach of these samples was constant at 28.

TABLE 3 Extrusion and Orientation Conditions Die Example ExtrudateTemperature Oriented Denier Roll A Roll B Roll C No. ID (° F.) Yarn ID(g/9,000 m) (° C.) (° C.) (° C.) 10 C1 370 C1-B  56.3 65 80 85 10 3 3703-1 55.0 70 75 105 10 6 370 6-1 55.1 71 75 105 11 Extrudate unsuitablefor orientation 12 2 405 2-2 55.3 80 100 105 12 5 402 5-2 55.6 80 100105 12 6 402 6-1 56.0 80 100 105

TABLE 4 Oriented Yarn Mechanical Properties Example Extrudate OrientedDenier Tenacity Elongation No. ID Yarn ID (g/9,000 m) (g/d) (%) 10 C1C1-B 56.3 4.72 24.9 10 3 3-1 55.0 4.69 25.8 10 6 6-1 55.1 4.47 24.4 12 22-2 55.3 4.92 25.4 12 5 5-2 55.6 4.65 24.8 12 6 6-1 56.0 4.98 24.2

It should be noted that the oriented yarns of Example 10 and Example 12described in Tables 3-4 exhibit good mechanical properties enabling themto be braided into a variety of useful surgical products includingsutures.

Braided sutures of USP size 6/0 to 1 were prepared using themultifilament yarns resulting from the yarn of Example 10 and Example12. These sutures showed an average high initial straight tensilestrength and high knot strength. Furthermore, they exhibited an in vivobreaking strength retention profiles in which all or at least most ofthe tensile strength was lost at 14 days. This characteristic isconsistent with a “fast absorbing suture.” The sutures made using theprocess of the present invention had excellent handling characteristicsand were essentially entirely absorbed in vivo within about 42 days;again consistent with a “fast absorbing suture.”

Example 11

Attempted Extrusion of the Resin of Example 8

In a manner similar to Example 10, attempts were made to extrude thepolymer melt-blend described in Example 8 to produce filaments withsuitable mechanical properties. Although a broad variety of conditionswere investigated, all attempts failed, most likely due to the lowmolecular weight nature of this particular resin (a weight averagemolecular weight of 38,000 Daltons).

Example 12

Extrusion and Orientation of the Resin of Example 9

In a manner similar to Example 10, the polymer melt-blend described inExample 9 was used to produce filaments and, thereafter, bio-absorbablemultifilament braided sutures.

The data for the characteristics of the resulting multifilament yarnsfor this Example 12 can be found in Table 4 above.

The yarns of this Example 12 exhibit good mechanical properties enablingthem to be braided into a variety of useful surgical products includingsutures.

Example 13

Braiding, Scouring, Hot Stretching and Annealing of Oriented Yarn

The yarns from Example 10 and Example 12 were braided, scoured in ethylacetate, hot stretched and annealed in a conventional manner. Theresulting annealed braid will be referred to as the annealed braid ofExample 13.

Example 14

Coating and Pliabilization of the Annealed Braids

The annealed braid of Example 13 was coated and pliabilized in aconventional manner.

Example 15

Needle Attachment, Packaging and Sterilization

The coated braid of Example 14 was packaged and ethylene oxidesterilized in a conventional manner.

Example 16

Analytical Results

In general, the resins and fibers of the present invention werecharacterized for chemical composition by Nuclear Magnetic Resonance(NMR); for molecular weight by inherent viscosity inhexafluoroisopropanol at 0.1 g/dL at 25° C., and/or gel permeationchromatography (GPC); and for morphology by X-ray diffraction, anddifferential scanning calorimetry (DSC). Analysis was performed onfibers prior to annealing, after annealing, and often after EOsterilization.

Example 17

Mechanical Properties and In Vitro Testing

The size 2/0 EO sterilized coated braids of Example 15 were tested formechanical properties and underwent in vitro testing. The processesemployed will now be described. The selected lot was tested formechanical properties using an INSTRON tensile testing machine, Model5544 fitted with an appropriate load cell. The articles were placed in afixture designed to appropriately grip and the force-to-break wasrecorded as “Zero-Day Breaking Strength”.

Samples of the EO sterilized coated braids of Example 15 were placed incontainers filled with a suitable amount of phosphate buffer at pH 7.27.The containers were then incubated at 37° C. and a representative samplesize, typically eight, was retrieved periodically for mechanicaltesting. The incubated articles were tested for their mechanicalproperties using an INSTRON tensile testing machine in a fashion similarto the above mentioned method. The force-to-break was recorded as“Breaking Strength”. The ratio of “Breaking Strength” to “Zero-DayBreaking Strength” was calculated and reported as “Breaking StrengthRetention” for each time period.

The in vitro testing results of the size 2/0 EO sterilized coated braidsof Example 15 are shown directly below in Table 5.

TABLE 5 Braids of Example 15, Test Incubation Time in pH 7.27 Buffer at37° C. Number 0 Day 5 Day 7 Day 10 Day 14 Day 17 Day 1 11.72 7.76 6.072.32 0.24 0.06 2 11.33 7.85 6.09 2.36 0.28 0.10 3 10.81 8.06 5.67 2.280.10 0.12 4 11.11 7.92 6.14 2.18 0.32 0.09 5 11.31 7.52 6.11 1.60 0.210.09 6 11.33 8.30 5.63 2.02 0.14 0.05 7 10.77 7.65 6.53 1.86 0.27 0.10 811.00 8.20 6.12 1.97 0.12 0.13 Average 11.17 7.91 6.05 2.07 0.21 0.09S.D. 0.32 0.27 0.29 0.26 0.08 0.03

The in vitro testing results of the size 2/0 EO sterilized coated braidsof Example 15, expressed as percent strength remaining, are showndirectly below in Table 6.

TABLE 6 Percent Strength Remaining After Incubation in pH 7.27 Buffer at37° C. for the Indicated Times 0 Day 5 Day 7 Day 10 Day 14 Day 17 DayBraids of 100 71 54 19 1.9 0.8 Example 15

Example 18

In Vivo Breaking Strength Retention Testing

The size 2/0, EO sterilized, coated braids of Example 15, underwent invivo testing to assess breaking strength retention post-implantation.The testing was conducted in a conventional manner. The testing resultsare shown directly below in Table 7.

TABLE 7 Braids of Example 15, Strength (in lbs) of Size 2/0 Sutures Testat the Indicated Time Post-Implantation Number 0 Day 5 Day 7 Day 10 Day14 Day 17 Day 1 10.54 7.44 6.22 3.02 0.10 — 2 10.86 7.41 6.01 2.28 0.14— 3 10.79 7.65 6.10 2.90 0.18 — 4 10.33 7.37 6.14 2.91 0.27 — 5 10.067.72 6.59 3.16 0.25 — 6 10.86 7.79 6.32 2.80 0.12 — 7 11.10 7.46 6.042.57 0.15 — 8 10.56 7.73 5.87 3.07 0.11 — Average 10.64 7.57 6.16 2.840.17 0.00 S.D. 0.33 0.17 0.22 0.29 0.06 0.00

The in vivo testing results of the size 2/0 EO sterilized coated braidsof Example 15, expressed as percent strength remaining, are showndirectly below in Table 8.

TABLE 8 Percent Strength Remaining Post-Implantation for the IndicatedTimes 0 Day 5 Day 7 Day 10 Day 14 Day 17 Day Braids of 100 71 58 27 1.60.0 Example 15

Agreement between the in vitro testing results and the in vivo testingresults was good, as shown in the Table 9 below:

TABLE 9 Braids of Percent Strength Remaining Example 15 0 Day 5 Day 7Day 10 Day 14 Day 17 Day In Vitro 100 71 54 19 1.9 0.8 In Vivo 100 71 5827 1.6 0.0

Example 19

In Vivo Total Absorption

The coated braids of Example 14 underwent in vivo testing to assessabsorption and tissue reaction characteristics. The testing wasconducted in a conventional manner.

Example 20

Information for MW Data on Various Braids

Additional data for the inventive blends and devices made of theinventive blends is shown in Tables 10-12.

TABLE 10 Processing Data of EO-Sterilized Size 2/0 Triclosan-CoatedSutures Blend Die Temp Yarn tenacity Coated Polymer IV [° F.] [gpd] Lot# P20-1 1.23 421 6.60 C20-1 P20-1 1.23 411 5.10 C20-2 P20-2 1.18 4115.40 C20-3 P20-2 1.18 431 5.90 C20-4 P12-3 1.24 421 6.10 C20-5 P20-31.24 431 6.20 C20-6 P20-4 1.32 441 5.90 C20-7 P20-4 1.32 451 5.20 C20-8P20-3 1.24 441 4.90 C20-9

TABLE 11 Molecular Weight Testing of Non-Sterile Braid Sample M_(w)M_(n) M_(z) M_(w)/ IV Description (10³ g/mol) (10³ g/mol) (10³ g/mol)M_(n) (dL/g) C20-1 43.3 15.6 76.6 2.79 0.99 C20-2 43.1 15.8 76.7 2.730.98 C20-3 40.6 15.7 70.9 2.60 0.97 C20-4 41.1 16.2 71.0 2.54 0.94 C20-546.4 17.9 79.1 2.60 0.98 C20-6 44.5 15.9 79.1 2.80 0.99 C20-7 46.2 16.781.4 2.78 1.01 C20-8 43.3 17.1 74.7 2.54 0.97 C20-9 45.9 17.8 79.5 2.600.99

TABLE 12 Molecular Weight Testing of EO-Sterilized Braid Sample M_(w)M_(n) M_(z) M_(w)/ IV Description (10³ g/mol) (10³ g/mol) (10³ g/mol)M_(n) (dL/g) C20-1S 43.4 16.5 75.9 2.65 0.95 C20-2S 43.3 16.0 76.2 2.710.96 C20-3S 41.4 15.6 72.9 2.66 0.93 C20-4S 39.6 15.0 71.1 2.65 0.92C20-5S 46.4 18.0 79.6 2.58 0.97 C20-6S 45.2 17.3 78.9 2.61 0.96 C20-7S46.1 17.3 81.0 2.67 0.97 C20-8S 46.0 20.7 84.9 2.23 0.94 C20-9S 44.817.1 78.5 2.62 0.96

Example 21

Strength and In Vitro Performance Comparisons

Polymeric blends of the subject invention based on 10/90poly(L(−)-lactide-co-glycolide) were made into braided sutures ofvarious sizes to compare against commercial sutures prepared from thesame base resin, 10/90 poly(L(−)-lactide-co-glycolide). These commercialsutures had been treated to achieve an accelerated absorption profile:essentially no strength remaining at 14 days post-implantation andessentially absorbed at 42 days post-implantation. Breaking strengthvalues obtained at various times of incubation in vitro under thetesting conditions of 37° C. and pH 7.27 were obtained. Comparison ofthe initial breaking strength and strength after five days of in vitroincubation at 37° C. and pH 7.27 of variously sized sutures of thepresent invention and of similar sutures consisting essentially of thefirst polymeric component are shown in Table 13. The latter arecommercial 10/90 poly(L(−)-lactide-co-glycolide) sutures that had beentreated as part of the manufacturing process to achieve an acceleratedabsorption profile of essentially no strength remaining at 14 dayspost-implantation and essentially absorbed at 42 days post-implantation.

TABLE 13 Comparison of the Breaking Strength of Variously Sized Suturesof the Present Invention and of Similar Sutures Consisting Essentiallyof the First Polymeric Component; Initial Strength and Strength afterFive Days of In Vitro Incubation at 37° C. and pH 7.27 Similar SutureConsisting Suture of the Present Essentially of the First InventionPolymeric Component Strength at Strength at USP Initial 5 Days Initial 5Days Suture Strength Incubation Strength Incubation Size [lbs] [lbs][lbs] [lbs] Size 1 23.70 17.02 18.23 9.26 Size 0 18.60 12.84 13.33 6.92Size 2/0 13.80 9.85 9.71 4.90 Size 3/0 8.64 6.66 6.36 3.45 Size 4/0 5.904.20 4.13 2.27 Size 5/0 3.41 2.33 2.36 1.15 Size 6/0 1.32 0.90 1.10 0.62Size 7/0 0.35 Size 8/0 0.26

Diameter measurements on the sutures shown above were approximately 19,16, 13, 10, 8, 6, 3.3 2.4 and 1.8 mils for the sutures sizes 1, 0, 2/0,3/0, 4/0, 5/0, 6/0, 7/0 and 8/0, respectively.

The novel bioabsorbable polymeric compositions and blends of the presentinvention have many advantages including providing medical devices thathave improved mechanical properties with precisely controllableabsorption rates. The advantages of the novel polymer blends of thepresent invention are also apparent from the graphs of data in FIGS.4-7.

Although this invention has been shown and described with respect todetailed embodiments thereof, it will be understood by those skilled inthe art that various changes in form and detail thereof may be madewithout departing from the spirit and scope of the claimed invention. Itwill be understood that the embodiments described herein are merelyexemplary and that a person skilled in the art may make many variationsand modifications, including but not limited to those discussedhereinabove, without departing from the spirit and scope of the presentinvention. All such variations and modifications are intended to beincluded within the scope of the invention as defined in the appendedclaims.

We claim:
 1. A suture, comprising an absorbable polymer blend, the blendcomprising: a mixture of a polymer and an oligomer, wherein the polymerhas a weight average molecular weight higher than the weight averagemolecular weight of the oligomer, and wherein the weight averagemolecular weight of the oligomer is about 1,400 Daltons to about 5,200Daltons, wherein at least about 100% of the absorbable oligomer isend-capped on both ends by carboxylic acid groups and about 0% of thepolymer is end-capped by carboxylic acid groups, and wherein a suturemade from said blend and having a size has a pre-implantation strengthequivalent to or greater than the pre-implantation strength of a similarsuture one size larger, said similar suture consisting essentially ofthe first component, wherein said suture and said similar suture have asubstantially equivalent time to achieve zero mechanical strength. 2.The suture of claim 1, wherein the polymer blend has an inherentviscosity of about 0.5 dL/g to about 1.8 dL/g.
 3. The suture of claim 1,wherein the weight average molecular weight of the polymer blend isabout 18,000 Daltons to about 100,000 Daltons.
 4. The suture of claim 1,said device coated with a medically useful substance.
 5. The suture ofclaim 1, wherein at least a part of the suture comprises a plurality ofyarns or filaments.
 6. The suture of claim 1, wherein the suture is amonofilament.
 7. The suture of claim 1, wherein said suture comprises aplurality of filaments, the filaments a blend ofpoly(lactide-co-glycolide) copolymer comprising about 88 wt. % to about92 wt. % of polymerized glycolide and about 8 wt. % to about 12 wt. % ofpolymerized lactide, wherein the suture has a diameter of about 19 mils,a minimum pre-implantation tensile strength of about 20 pounds, aminimum tensile strength of about 12 pounds at 5 days post-implantation,substantially no tensile strength at 14 days post-implantation, andwherein the suture is substantially absorbed in about 42 dayspost-implantation.
 8. The suture of claim 1, wherein said suturecomprises a plurality of filaments, the filaments comprising a blend ofpoly(lactide-co-glycolide) copolymer, said copolymer comprising about 88wt. % to about 92 wt. % of polymerized glycolide and about 8 wt. % toabout 12 wt. % of polymerized lactide, wherein the suture has a diameterof about 16 mils, a minimum pre-implantation tensile strength of about15 pounds, a minimum tensile strength of about 9.5 pounds at 5 dayspost-implantation, from substantially no tensile strength to about 5% ofthe pre-implantation tensile strength at 14 days post-implantation, and,wherein the suture is substantially absorbed in about 42 dayspost-implantation.
 9. The suture of claim 1, wherein said suturecomprises a plurality of filaments, the filaments comprising a blend ofpoly(lactide-co-glycolide) copolymer, said copolymer comprising about 88wt. % to about 92 wt. % of polymerized glycolide and about 8 wt. % toabout 12 wt. % of polymerized lactide, wherein the suture has a diameterof about 13 mils, a minimum pre-implantation tensile strength of about11 pounds, a minimum tensile strength of about 7 pounds at 5 dayspost-implantation, substantially no tensile strength at 14 dayspost-implantation, and, wherein the suture is substantially absorbed inabout 42 days post-implantation.
 10. The suture of claim 1, wherein saidsuture comprises a plurality of filaments, the filaments comprising ablend of poly(lactide-co-glycolide) copolymer, said copolymer comprisingabout 88 wt. % to about 92 wt. % of polymerized glycolide and about 8wt. % to about wt. % 12 of polymerized lactide, wherein the suture has adiameter of about 10 mils, a minimum pre-implantation tensile strengthof about 7.5 pounds, a minimum tensile strength of about 4.5 pounds at 5days post-implantation, substantially no tensile strength at 14 dayspost-implantation, and, wherein the suture is substantially absorbed inabout 42 days post-implantation.
 11. The suture of claim 1, wherein saidsuture comprises a plurality of filaments, the filaments comprising ablend of poly(lactide-co-glycolide) copolymer, said copolymer comprisingabout 88 wt. % to about 92 wt. % of polymerized glycolide and about 8wt. % to about 12 wt. % of polymerized lactide, wherein the suture has adiameter of about 8 mils, a minimum pre-implantation tensile strength ofabout 4.6 pounds, a minimum tensile strength of about 3 pounds at 5 dayspost-implantation, substantially no tensile strength at 14 dayspost-implantation, and, wherein the suture is substantially absorbed inabout 42 days post-implantation.
 12. The suture of claim 1, wherein saidsuture comprises a plurality of filaments, the filaments comprising ablend of poly(lactide-co-glycolide) copolymer, said copolymer comprisingabout 88 wt. % to about 92 wt. % of polymerized glycolide and about 8wt. % to about 12 wt. % of polymerized lactide, wherein the suture has adiameter of about 6 mils, a minimum pre-implantation tensile strength ofabout 2.6 pounds, a minimum tensile strength of about 1.6 pounds at 5days post-implantation, substantially no tensile strength at 14 dayspost-implantation, and, wherein the suture is substantially absorbed inabout 42 days post-implantation.
 13. The suture of claim 1, wherein saidsuture comprises a plurality of filaments, the filaments comprising ablend of poly(lactide-co-glycolide) copolymer, said copolymer comprisingabout 88 wt. % to about 92 wt. % of polymerized glycolide and about 8wt. % to about 12 wt. % of polymerized lactide, wherein the suture has adiameter of about 3.3 mils, a minimum pre-implantation tensile strengthof about 1.2 pound, a minimum tensile strength of about 0.75 pounds at 5days post-implantation, substantially no tensile strength at 14 dayspost-implantation, and, wherein the suture is substantially absorbed inabout 42 days post-implantation.
 14. The suture of claim 1, wherein saidsuture comprises a plurality of filaments, the filaments comprising ablend of poly(lactide-co-glycolide) copolymer, said copolymer comprisingabout 88 wt. % to about 92 wt. % of polymerized glycolide and about 8wt. % to about 12 wt. % of polymerized lactide, wherein the suture has adiameter of about 2.4 mils, a minimum pre-implantation tensile strengthof about 0.53 pounds, a minimum tensile strength of about 0.40 pounds at5 days post-implantation, substantially no tensile strength at 14 dayspost-implantation, and, wherein the suture is substantially absorbed inabout 42 days post-implantation.
 15. The suture of claim 1, wherein saidsuture comprises a plurality of filaments, the filaments comprising ablend of poly(lactide-co-glycolide) copolymer, the copolymer comprisingabout 88 wt. % to about 92 wt. % of polymerized glycolide and about 8wt. % to about 12 wt. % of polymerized lactide, wherein the suture has adiameter of about 1.8 mils, a minimum pre-implantation tensile strengthof about 0.45 pounds, a minimum tensile strength of about 0.30 pounds at5 days post-implantation, substantially no tensile strength at 14 dayspost-implantation, and, wherein the suture is substantially absorbed inabout 42 days post-implantation.